2016
DOI: 10.1007/s00401-016-1620-7
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Abstract: Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 9… Show more

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Cited by 128 publications
(102 citation statements)
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“…In univariable time‐to‐VTE regression, the IDH1 mutation predicted a lower risk of VTE (hazard ratio [HR] = 0.11; 95% CI, 0.01–0.80; P = 0.029), and this prevailed after multivariable adjustment for glioblastoma and age (Models #1 and #2, Table ). Thus, these clinical data externally validate previous findings demonstrating that mutant IDH1 is a predictor of low VTE risk in patients with primary brain tumors . Based on a mouse model, Unruh et al .…”
Section: Resultssupporting
confidence: 85%
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“…In univariable time‐to‐VTE regression, the IDH1 mutation predicted a lower risk of VTE (hazard ratio [HR] = 0.11; 95% CI, 0.01–0.80; P = 0.029), and this prevailed after multivariable adjustment for glioblastoma and age (Models #1 and #2, Table ). Thus, these clinical data externally validate previous findings demonstrating that mutant IDH1 is a predictor of low VTE risk in patients with primary brain tumors . Based on a mouse model, Unruh et al .…”
Section: Resultssupporting
confidence: 85%
“…Based on a mouse model, Unruh et al . proposed that IDH1 mutation leads to decreased serum calcium levels with subsequent inhibition of platelet activation, thereby preventing VTE . However, we were not able to confirm a statistically significant association between IDH1 status and serum calcium concentrations in primary brain tumor patients (Table ).…”
Section: Resultscontrasting
confidence: 62%
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“…Similarly, we expect that major insights will come from a detailed comparison of how distinct molecular subtypes or genetic drivers in cancer cells may differentially sculpt their microenvironment during the course of cancer progression, as already indicated from several studies discussed herein (Miroshnikova et al, 2016; Osswald et al, 2015; Phoenix et al, 2016; Unruh et al, 2016). Indeed, there are genetic subsets of glioma that do display efficacy to standard of care cytotoxic therapy, for example, those with mutant IDH, or co-deletion of 1p and 19q in oligodendrogliomas.…”
Section: Conclusion and Future Perspectivesmentioning
confidence: 69%
“…A recent study has investigated whether patients with wild‐type IDH1/2 glioblastoma are more likely to develop VTE. Interestingly, patients harboring IDH1/2 mutations did not develop VTE neither in a discovery nor in a validation cohort, both consisting of approximately 150 patients 56. Furthermore, only 2% of the tumors with IDH1/2 mutation showed intratumoral microthrombi versus 86% in wild‐type IDH1/2 tumors.…”
Section: Tumor‐specific Geneticsmentioning
confidence: 98%